We have developed a plant-based adjuvant/carrier:antigen fusion technology that offers significant advantages over conventional injectable vaccination regimes including: safety, mucosal efficacy, ease of delivery, rapid scalability, unlimited supply potential, and cost-savings. This technology has significant potential in contributing to biodefense strategies protecting both military and civilian populations currently threatened with biological weapons of mass destruction. Pneumonic plague is one of the most likely terrorist weapons for which no vaccine of proven efficacy is currently available. Since mucosal administration is considered the most effective route for conferring protection against a pneumonic form of the disease, the lack of an effective mucosal adjuvant acceptable for human use presents a significant hurdle. BioDefense Technologies, Inc. brings two new technologies to vaccine development that are significantly relevant for plague: 1) a new non-toxic mucosal adjuvant/carrier, MAC1, that functions to effectively deliver fused antigens to mucosal immune-responsive tissues and shows intranasal adjuvancy in mice equivalent to co-administered cholera toxin adjuvant and 2) transgenic plant-based bioproduction that addresses issues of safety, scale, and cost of recombinant subunit vaccines. A fusion of the Yersinia pestis protective antigens, F1 and V, appear the most promising for subunit vaccines. We propose to produce MAC1: F1:V fusion protein in transgenic tobacco. Purified MAC1:F1:V will be intranasally delivered to mice and mucosal and systemic responses will be used to assess vaccine efficacy. MAC1:F1:V adjuvancy in mice will be compared to that of co-administered F1:V and cholera toxin. These studies will provide the foundation for developing fusion proteins in transgenic plants, scale-up production protocols for MAC1:F1:V and conducting pneumonic plague challenges during Phase II. Our plant-based MAC1:antigen fusion technology is quite modular, easily purified and well suited for rapid development of new vaccines to counter genetically modified plague pathogens and newly emerging biowarfare agents. Furthermore, our MAC1:antigen technology has potential applications as a mucosal adjuvant/delivery molecule for developing non-defense related vaccines directed at HIV, cancer, and autoimmune diseases.